Antibiotics are the most exploited microbial products in the biotechnology industry. Currently, the technology used for the treatment of veterinary infections and in the promotion of animal growth is based on conventional antibiotics. For example, it was shown that the bacteria Bacillus subtilis, Escherichia coli and Salmonella enteritidis that cause infections in chickens are resistant to known antimicrobial agents such as tetracycline, nalidixic acid, ampicillin, and others (see Ribeiro, A. R., Kellermann, A., Santos, L. R., Nascimento V. P. 2008. Resistência antimicrobiana em Salmonella enteritidis isoladas de amostras clínicas e ambientais de frangos de corte e matrizes pesadas. Arq. Bras. Med. Vet. Zootec. 60 (5): 1259-1262). Such conventional antibiotics are also used for the treatment of human infections. This overlay leads to the emergence of a large increase of resistant strains, which complicates the treatment of infections in humans. Thus, the isolation of new chemical entities with antimicrobial activity for exclusive use in animals will provide significant benefits in raising animals for slaughter, said entities being used as growth promoters and in the treatment of veterinary infections, and these benefits will result not only in increased earnings for producers, but also in the exclusion of the use of current antibiotics in animals consumed by men.
The emergence of resistant bacteria occurred soon after the clinical use of antimicrobial agents like penicillin Since then it became clear that for each new antimicrobial agent that is available on the market a bacteria resistant to these new agents quickly appears, and the rapidity with which this resistance is developed is proportional to the size of the use of new drugs. Recently it was found that the use of antimicrobials in animals used to feed men has caused the emergence of pathogenic bacteria resistant to the antibiotics used to treat infections in humans (for more details, see Wegener H. C. et al. “Public Health Impacts of the Use of Antimicrobials in Food Animals”, Proceedings of the WBC Congress, 23rd World Buiatrics Congress, Quebec City, Canada, 2004).
The antimicrobial agents can be natural or synthetic substances which inhibit or kill microorganisms, including bacteria. Currently there are over 15 different classes of antimicrobial substances, which differ in chemical structure and mechanism of action, causing them to be highly specific in the treatment of specific pathogens. The emergence of antimicrobial agents was the great victory of the 20th century in the fields of medicine, veterinary medicine and agriculture, not only for its therapeutic value, but also for its property to promote the growth of plants and animals when used in sub-therapeutic amounts (see “Use of antimicrobials outside human medicine and resultant antimicrobial resistance in humans”, Fact sheet No. 268, 01/2002, available on the Web at http://www.who.int/mediacentre/factsheets/fs268/en/).
The problems of the use of antibiotics as antimicrobial agents for the treatment of humans and animals have assumed such a strong position that governmental authorities of different countries have not only promoted researches to minimize the impact of resistance of pathogenic bacteria to existing antibiotics, but also worked in campaigns to educate the public to the increasing risks of this increase in resistance, aiming at reducing the use of antibiotics in animals, especially in subtherapeutic quantities to promote animal growth and improve the yield of meat production. Examples of these government initiatives are: (1) the Report “Overarching AMR” in the UK, published in 2004 (see “Overview of Antimicrobial Usage and Bacterial Resistance in Selected Human and Animal Pathogens in the UK:2004”, available on the Web at http://www.dardni.gov.uk/index/publications/pubs-dard-animal-health/pubs-vet-meds.htm) and (2) the work performed by San Martin, B. et al. Funded by the Chilean National Fund for Scientific and Technological Development (see San Martín, B. et al. “Evaluation of Antimicrobial Resistance Using Indicator Bacteria Isolated from Pigs and Poultry in Chile”, Intern J Appl Res Vet Med, Vol. 3, No. 2, 171-178, 2005).
One of the most promising paths in the quest to achieve this goal is to use a biological material that is effective as an antimicrobial agent and as a growth promoter in animals, especially in chickens and pigs. In 2004 the group of Dal-Soo identified (see Dal-Soo, K. et al. “Paenibacillus elgii sp. nov., with broad antimicrobial activity”, International Journal of Systematic and Evolutionary Microbiology 54, 2031-2035, 2004), two strains (SD17 and SD18) which were classified as a new spore-forming bacteria with broad antimicrobial activity, said strains being isolated from roots of Perilla frutescens. Later, Dal-Soo, K. ela al. (see Dal-Soo, K. et al. “Paenibacillus elgii SD17 as a Biocontrol Agent Against Soil-borne Turf Diseases”, Plant Pathol. J. 21(4):328-333, 2005) identified in strain SD17 a broad-spectrum antimicrobial activity against diseases caused by microorganisms in grass. Laboratory tests conducted with a granule formulation prepared with the fermentation broth of Paenibacillus elgii SD17 showed efficacy similar to the commercial fungicides, while field tests with the same formulation showed an efficacy lower than the commercial fungicides. Despite these results on the field, the authors considered the granule formulation made with Paenibacillus elgii SD17 an appropriate biocontrol agent.
The search for antimicrobial agents for the treatment of plant diseases caused by microorganisms also resulted in the composition disclosed in WO 09045023, which composition is based on the use of superabsorbent polymers as a support for (a) beneficial microorganisms which inhibit the growth of pathogens in plants and (b) a nutrient medium for said beneficial microorganism. On page 13, line 2 of document WO09045023 Paenibacillus elgii SD17 is mentioned as one of the beneficial microorganisms.
EP 1788074 describes new strains belonging to the genus Paenibacillus and their use, or the culture of these new strains to control plant diseases. These new strains are Paenibacillus sp. BS-0048, Paenibacillus sp. BS-0074, Paenibacillus polymyxa BS-0105 and Paenibacillus sp. BS-0277. This document describes formulations comprising the crude fermentation extract using the new strains and/or compounds produced in these fermentations, such compounds called Fusaricidin A, Fusaricidin B, compound 3 and compound 4 with their chemical formulas defined in claim 3.
As can be seen in the prior art mentioned above there is no mention of the isolation of proteins or peptides with protective activity and promotes of plant growth obtained from Paenibacillus sp. And also, there is no report about getting a protein or a peptide derived from Paenibacillus sp. with antimicrobial activity and/or growth promoter in animals intended for slaughter for human consumption. Such proteins or peptides bring an important advance in the search for alternatives to reduce the increasing resistance of pathogenic bacteria to antibiotics in use for the treatment of microbial infections in humans.